This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Neural Substrates of Age-related Cognitive Decline in Monkeys The rhesus monkey is a model of normal human aging that allows cognitive testing to be followed by optimal preservation of brain tissue for study. This projects tests the hypothesis that age-related cognitive decline results from a cascade of mild degenerative changes beginning with inflammation in white matter followed by functional and then structural changes in neurons. This is a longitudinal project that follows a group of 12 middle aged female rhesus monkeys for five years beginning between 13 and 15 years of age. Regular behavioral assessment is conducted to identify the rate of age-related cognitive decline and to determine how this differs among subjects in order to differentiate between monkeys that age "successfully" and those that are relatively "unsuccessful". Regular MRI scans, blood samples and CSF samples are collected to assess different markers of aging. At the end of five years the brain tissue samples will be used to identify changes responsible for cognitive decline. As the degree of cognitive impairment is mild at 13 - 15 but high by 18 - 20 years of age, these data will allow us to identify brain changes associated with the rate of cognitive decline with the goal of designing therapeutic interventions aimed at slowing or reversing cognitive decline.